Safety Study of Preoperative Sunitinib and Radiation in Soft Tissue Sarcoma (SunRaSe)

August 25, 2017 updated by: Peter Hohenberger, Heidelberg University

Phase 1 Trial of Concurrent Sunitinib and Radiation Therapy as Preoperative Treatment for Locally Advanced or Recurrent Soft Tissue Sarcoma.

To evaluate the toxicity of sunitinib concurrently given with irradiation for preoperative treatment of locally advanced or recurrent soft tissue sarcoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Although the introduction of multimodal treatment of soft tissue sarcoma resulted in great progress in STS treatment, local failure still occurs in 10-20% of STS patients. Therefore further improvement of local and systemic treatment is needed in order to achieve tumor control and limb salvage. The proposed study treatment will combine external beam radiation and orally administered sunitinib.

Sunitinib is a multiple receptor tyrosine kinase (RTK) inhibitor with anti-angiogenic and anti-tumoral properties. For their key role in tumor development, RTKs are regarded as excellent targets for cancer chemotherapy. External beam radiation is widely used as neoadjuvant treatment for locally advanced soft tissue sarcoma.

The concurrent application of anti-angiogenic sunitinib appears reasonable, since STS are highly vascularized tumors and overexpression of VEGFR and other RTKs has been shown for various histologic soft tissue sarcoma subtypes. At first sight, the combination of antiangiogenic treatment and radiation seems to be contradictory, since anti-angiogenic treatment attacks tumor vasculature and radiation effects are decreased by hypoxia. Yet, in animal studies the concurrent application of radiation with tyrosine kinase inhibitors such as sunitinib or other antiangiogenic agents resulted in additive, if not synergistic antitumoral effects. These results can be explained by the superiority of the anti-tumoral activity of antiangiogenic agents over their hypoxia related, radiation weakening effects; or by the hypothesis of vascular normalization. It is well known that tumor vasculature is immature and ineffective in means of blood supply and oxygenation. In preclinical models, antiangiogenic agents balanced pro- and anti-angiogenic effectors which may result in maturation of tumor vasculature with improvement of blood flow and oxygen supply.

The combination of sunitinib as an anti-angiogenic and anti-proliferative agent thus might not only add the therapeutic effects of the RTK-inhibitor and external beam radiation but might additionally lead to a radiosensitizing effect due to tumor vessel normalization. The Purpose of this study is to assess the toxicity of the combined treatment and to gather preliminary data on treatment efficacy.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Saarow, Germany, 15526
        • HELIOS Klinikum Bad Saarow
      • Mannheim, Germany, 68167
        • University Medical Center Mannheim

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • histologically proven soft tissue sarcoma of any histology but GIST, Angiosarcoma, dermatofibrosarcoma protuberans, Ewing Sarcoma or Embryonal Rhabdomyosarcoma
  • patients with primary tumors OR with local recurrences who did not receive prior radiation therapy OR with solitary metastatic lesions may be included
  • complete resection after neoadjuvant treatment is expected
  • age of 18 or older
  • ECOG performance score 0 or 1
  • normal organ and bone marrow function
  • ability to give written informed consent

Exclusion Criteria:

  • medication with inhibitors or inducers of CYP3A4
  • prior therapy with tyrosine kinase inhibitors or conventional chemotherapy within 4 weeks before study inclusion
  • history of myocardial infarction, stroke or thromboembolic events
  • clinical signs of heart failure (NYHA 3 or 4)
  • anticoagulation with Vitamin K antagonists
  • acquired or hereditary coagulopathy
  • uncontrolled hypertension
  • uncontrolled intercurrent illness
  • women who are pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined Sunitinib and irradiation
Patients with locally advanced or recurrent soft tissue sarcoma will receive Sunitinib and irradiation as neoadjuvant treatment. Restaging and tumor resection will be performed 6 weeks after completion of sunitinib and irradiation.
Drug: Sunitinib

Patients will receive Sunitinib daily for 2 weeks prior to and then concurrently with irradiation as neoadjuvant treatment. Radiotherapy will be given as intensity modulated radiation therapy with a total dose of 50.4Gy in 28 fractions to each patient (5 1/2 weeks).

Sunitinib will be given in two dose levels. The first dose level will be 25mg Sunitinib per os daily. The second dose level will be 37.5mg sunitinib per os daily. A dose modification schedule according to a 3+3 design will be applied for patient accrual.

Other Names:
  • Radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the dose limiting toxicity and maximal tolerated dose of sunitinib given concurrently with irradiation as neoadjuvant treatment in soft tissue sarcoma.
Time Frame: 12 weeks
Toxicity of the study treatment will be documented according to CTCAE 4.0 during and until 4 weeks after study treatment.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the response to sunitinib given concurrently with radiation as neoadjuvant treatment in soft tissue sarcoma.
Time Frame: 6 weeks after completion of study treatment.
Imaging response will be determined according to RECIST criteria comparing magnetic resonance imaging performed prior to and 6 weeks after completion of study treatment. Pathologic response will be determined evaluating the the fraction of non-viable tumor in the resection specimen.
6 weeks after completion of study treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heidelberg University

Collaborators

German Research Foundation

Investigators

  • Principal Investigator: Peter Hohenberger, MD PhD, Heidelberg University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

December 21, 2011

First Submitted That Met QC Criteria

December 22, 2011

First Posted (Estimate)

December 23, 2011

Study Record Updates

Last Update Posted (Actual)

August 28, 2017

Last Update Submitted That Met QC Criteria

August 25, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GISG 03
  • 2007-002864-87 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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